Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, College of Pharmacy, College of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, Dalian Medical University, Dalian, 116044, People's Republic of China.
Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, College of Pharmacy, College of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, Dalian Medical University, Dalian, 116044, People's Republic of China.
Phytochemistry. 2022 Jan;193:112974. doi: 10.1016/j.phytochem.2021.112974. Epub 2021 Oct 12.
Intestinal commensal fungi are vital to human health, and their metabolites play a key role in the reciprocal relationship. In the present work, eighteen alkaloids and seven monoterpenoids were isolated from the fermentation of the human intestinal fungus Penicillium oxalicum SL2, including seven undescribed alkaloids (penicilloxalines A-G), three undescribed monoterpenoids (penicilloxalines H-J), and fifteen reported compounds. The structures of the isolated compounds were identified by HRESIMS, 1D and 2D NMR, electronic circular dichroism spectra and quantum chemical calculations. Some metabolites displayed moderate agonistic effects against the pregnane X receptor (PXR), whereas (6R)3,7-dimethyl-6,7-dihydroxy-2(Z)-octenoic acid displayed a significant agonistic effect against the farnesoid X receptor (FXR) with an EC value of 0.43 μM, which was verified by investigating FXR downstream target genes and proteins, such as small heterodimer partner 1 (SHP1), fibroblast growth factor (FGF), and bile salt export pump (BSEP).
肠道共生真菌对人类健康至关重要，其代谢产物在互惠关系中发挥着关键作用。本工作从人源肠道真菌草酸青霉 SL2 的发酵液中分离得到 18 个生物碱和 7 个单萜类化合物，包括 7 个未被描述的生物碱（penicilloxalines A-G）、3 个未被描述的单萜（penicilloxalines H-J）和 15 个已知化合物。通过高分辨质谱、一维和二维核磁共振、电子圆二色光谱和量子化学计算等方法鉴定了分离得到的化合物的结构。一些代谢产物对孕烷 X 受体（PXR）表现出中等的激动作用，而（6R）3,7-二甲基-6,7-二羟基-2(Z)-辛烯酸对法尼醇 X 受体（FXR）表现出显著的激动作用，EC 值为 0.43 μM，通过检测 FXR 下游靶基因和蛋白，如小异二聚体伴侣 1（SHP1）、成纤维细胞生长因子（FGF）和胆汁盐输出泵（BSEP），验证了这一作用。
